2-Hydroxyimino(thien-2-yl)acetic acid | 50382-21-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 英文名称: 2-Hydroxyimino(thien-2-yl)acetic acid
• 英文别名: 2-hydroxyimino-2-thiophen-2-ylacetic acid
• CAS: 50382-21-3
• 化学式: C₆H₅NO₃S
• 分子量: 171.177
• InChiKey: MRUYQGKJYNYKFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  98.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-Hydroxyimino(thien-2-yl)acetic acid 在 吡啶 、 碳酸氢钠 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 三氯乙腈 为溶剂， 生成 (4-Cyano-3-fluorophenoxy)-[[(2-hydroxyimino-2-thiophen-2-ylacetyl)amino]methyl]phosphinic acid
  参考文献：
  名称：

  Thiophenyl oxime-derived phosphonates as nano-molar class C beta-lactamase inhibitors reducing MIC of imipenem against Pseudomonas aeruginosa and Acinetobacter baumannii

  摘要：

  The preparation and characterization of a series of thiophenyl oxime phosphonate beta-lactamase inhibitors is described. A number of these analogs were potent and selective inhibitors of class C beta-lactamases from Pseudomonas aeruginosa and Enterobacter cloacae. Compounds 3b and 7 reduced the MIC of imipenem against an AmpC expressing strain of imipenem-resistant P. aeruginosa. A number of the title compounds retained micromolar potency against the class D OXA-40 beta-lactamase from Acinetobacter baumannii and at high concentrations compound 3b was shown to reduce the MIC of imipenem against a highly imipenem-resistant strain of A. baumanii expressing the OXA-40 beta-lactamase. In mice compound 3b exhibited phamacokinetics similar to imipenem. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.122
• 作为产物：
  描述：

  2-噻酚乙酯乙酸乙酯 在 吡啶 、 盐酸羟胺 、 水 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 生成 2-Hydroxyimino(thien-2-yl)acetic acid
  参考文献：
  名称：

  Thiophenyl oxime-derived phosphonates as nano-molar class C beta-lactamase inhibitors reducing MIC of imipenem against Pseudomonas aeruginosa and Acinetobacter baumannii

  摘要：

  The preparation and characterization of a series of thiophenyl oxime phosphonate beta-lactamase inhibitors is described. A number of these analogs were potent and selective inhibitors of class C beta-lactamases from Pseudomonas aeruginosa and Enterobacter cloacae. Compounds 3b and 7 reduced the MIC of imipenem against an AmpC expressing strain of imipenem-resistant P. aeruginosa. A number of the title compounds retained micromolar potency against the class D OXA-40 beta-lactamase from Acinetobacter baumannii and at high concentrations compound 3b was shown to reduce the MIC of imipenem against a highly imipenem-resistant strain of A. baumanii expressing the OXA-40 beta-lactamase. In mice compound 3b exhibited phamacokinetics similar to imipenem. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.122

文献信息

• 3-Acetoxymethyl cephalosporins having at position-7 a carboxy
  申请人：Glaxo Laboratories Limited

  公开号：US04144393A1

  公开（公告）日：1979-03-13

  3-Acetoxymethyl cephalosporin antibiotics in which the 7.beta.-acylamido group has the structure ##STR1## where R is thienyl, furyl or phenyl; R.sup.a is C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-7 cycloalkyl or phenyl, and R.sup.b is hydrogen, carboxy, C.sub.2 -C.sub.5 carbalkoxy or any of the groups designated for R.sup.a, or R.sup.a and R.sup.b together with the carbon atom to which they are attached form a C.sub.3-7 cycloalkylidene or cycloalkenylidene group; exhibit broad spectrum antibiotic activity characterized by particularly high activity against gram negative microorganisms, including those which produce .beta.-lactamases. The compounds, which are syn isomers or exist as mixtures of syn and anti isomers containing at least 90% of the syn isomer, have particularly high in vitro activity against strains of Escherichia coli. Haemophilus influenzae and Proteus organisms; and also shown unusually high activity against Pseudomonas organisms.

  这是描述3-乙酰氧甲基头孢菌素类抗生素的化合物，其中7-β-酰胺基团的结构为##STR1##其中R为噻吩基，呋喃基或苯基；R.sup.a为C.sub.1-4烷基，C.sub.2-4烯基，C.sub.3-7环烷基或苯基，R.sup.b为氢，羧基，C.sub.2-C.sub.5羧基烷氧基或R.sup.a指定的任何基团，或R.sup.a和R.sup.b与它们附着的碳原子一起形成C.sub.3-7环烷亚烷基或环烯亚烷基团；这些化合物表现出广谱抗生素活性，特别是对革兰氏阴性微生物具有高度活性，包括产生β-内酰胺酶的微生物。这些化合物是同构体或存在于同构体和反异构体的混合物中，其中至少含有90％的同构体，对大肠杆菌，流感嗜血杆菌和变形杆菌菌株表现出特别高的体外活性，并且对假单胞菌菌株也表现出异常高的活性。
• Penicillin antibiotics
  申请人：Glaxo Laboratories Limited

  公开号：US03991046A1

  公开（公告）日：1976-11-09

  The invention provides novel antibiotic compounds which are 6.beta.-acylamidopenam-3-carboxylic acids and non-toxic derivatives thereof, characterized in that the acylamido group has the structure ##EQU1## WHERE R is a hydrogen atom or an organic group and R.sup.a is a hydrogen atom or an acyl group. The compounds are syn isomers or exist as mixtures containing at least 75% of the syn isomer. These antibiotic compounds possess high antibacterial activity against a range of gram positive and gram negative organisms coupled with particularly high stability to .beta.-lactamases produced by various gram negative organisms. The invention is also concerned with the administration of the compounds.

  本发明提供了一种新型抗生素化合物，它们是6-β-酰胺基青霉烯-3-羧酸及其非毒性衍生物，其特征在于酰胺基具有以下结构：##EQU1## 其中R是氢原子或有机基团，R.sup.a是氢原子或酰基。这些化合物是同构体或存在至少75%的同构体混合物。这些抗生素化合物对一系列革兰氏阳性和革兰氏阴性微生物具有高抗菌活性，并具有特别高的稳定性，能够抵御各种革兰氏阴性微生物产生的β-内酰胺酶。本发明还涉及这些化合物的管理。
• Syn isomers of cephalosporins having .alpha.-hydroximino- or
  申请人：Glaxo Laboratories Limited

  公开号：US04209616A1

  公开（公告）日：1980-06-24

  The invention provides novel antibiotic compounds which are 7.beta.-acylamidoceph-3-em-4-carboxylic acids, and non-toxic derivatives thereof, and 6.beta.-acylamidopenam-3-carboxylic acids, and non-toxic derivatives thereof, characterized in that the acylamido group has the structure ##STR1## where R is a hydrogen atom or an organic group and R.sup.a is a hydrogen atom or an acyl group. The compounds are syn isomers or exist as mixtures containing at least 75% of the syn isomer. These antibiotic compounds possess high antibacterial activity against a range of gram positive and gram negative organisms coupled with particularly high stability to .beta.-lactamases produced by various gram negative organisms. The invention is also concerned with the administration of the compounds.

  本发明提供了新的抗生素化合物，它们是7-β-酰胺基头孢-3-酰基-4-羧酸和其非毒性衍生物，以及6-β-酰胺基青霉烷-3-羧酸和其非毒性衍生物，其特征在于酰胺基具有以下结构：##STR1## 其中R是氢原子或有机基团，R.sup.a是氢原子或酰基。这些化合物是同构体或存在至少75％同构体的混合物。这些抗生素化合物对一系列革兰氏阳性和革兰氏阴性微生物具有高度的抗菌活性，并具有特别高的稳定性，能够抵抗各种革兰氏阴性微生物产生的β-内酰胺酶。本发明还涉及该化合物的使用。
• 3-Carbamoyloxymethyl or
  申请人：Glaxo Laboratories Limited

  公开号：US04095021A1

  公开（公告）日：1978-06-13

  Cephalosporin antibiotics in which the 7.beta.-acylamido group has the structure ##STR1## (where R is thienyl or furyl; R.sup.a and R.sup.b are each selected from hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-7 cycloalkyl, phenyl, naphthyl, thienyl, furyl, carboxy, C.sub.2-5 alkoxycarbonyl and cyano, or R.sup.a and R.sup.b together with the carbon atom to which they are attached form a C.sub.3-7 cycloalkylidene or cycloalkenylidene group; and m and n are each 0 or 1 such that the sum of m and n is 0 or 1) exhibit broad spectrum antibiotic activity characterized by particularly high activity against gram negative microorganisms, including those which produce .beta.-lactamases. The compounds, which are syn isomers or exist as mixtures of syn and anti isomers containing at least 90% of the syn isomer, have particularly high in vitro activity against strains of Escherichia coli, Haemophilus influenzae and Proteus organisms; compounds wherein at least one of R.sup.a and R.sup.b is other than hydrogen have also shown unusually high activity against Pseudomonas organisms. Important compounds of the above type include those in which the 7.beta.-acylamido group is a syn-2-carboxymethoxy-2-(fur-2-yl)acetamido, syn-2-(2-carboxyprop-2-yloxyimino)-2-(fur-2-yl)acetamido or syn-2-(1-carboxycyclopent-1-yloxyimino)-2-(fur-2-yl)acetamido group.

  7-β-酰胺基头孢菌素，其结构中的7-β-酰胺基团具有以下结构：##STR1##（其中R为噻吩基或呋喃基；R.sup.a和R.sup.b分别选自氢，C.sub.1-4烷基，C.sub.2-4烯基，C.sub.3-7环烷基，苯基，萘基，噻吩基，呋喃基，羧基，C.sub.2-5烷氧基羰基和氰基，或R.sup.a和R.sup.b与它们附着的碳原子形成C.sub.3-7环烷基亚甲基或环烯基亚甲基基团；m和n各为0或1，使m和n的和为0或1），表现出广谱抗生素活性，特别是对革兰氏阴性微生物，包括产生β-内酰胺酶的微生物具有特别高的活性。这些化合物是同构体或存在于至少90％为同构体的同和反异构体混合物，对大肠杆菌，流感嗜血杆菌和变形杆菌的菌株具有特别高的体外活性；其中至少有一个R.sup.a和R.sup.b不是氢的化合物也表现出对铜绿假单胞菌的异常高活性。上述类型的重要化合物包括其中7-β-酰胺基团为同-2-羧甲氧基-2-（呋喃-2-基）乙酰氨基，同-2-（2-羧基丙-2-氧基亚氨基）-2-（呋喃-2-基）乙酰氨基或同-2-（1-羧环戊-1-氧基亚氨基）-2-（呋喃-2-基）乙酰氨基基团的化合物。
• 7-(Carboxy substituted .alpha.-etherified oximino arylacetamido)
  申请人：Glaxo Laboratories Limited

  公开号：US04103084A1

  公开（公告）日：1978-07-25

  Cephalosporin antibiotics in which the 7.beta.-acylamido group has the structure ##STR1## (where R is thienyl or furyl; R.sup.a and R.sup.b are each selected from hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-7 cycloalkyl, phenyl, naphthyl, thienyl, furyl, carboxy, C.sub.2-5 alkoxycarbonyl and cyano, or R.sup.a and R.sup.b together with the carbon atom to which they are attached form a C.sub.3-7 cycloalkylidene or cycloalkenylidene group; and m and n are each 0 or 1 such that the sum of m and n is 0 or 1) exhibit broad spectrum antibiotic activity characterized by particularly high activity against gram negative microorganisms, including those which produce .beta.-lactamases. The compounds, which are syn isomers or exist as mixtures of syn and anti isomers containing at least 90% of the syn isomer, have particularly high in vitro activity against strains of Escherichia coli, Haemophilus influenzae and Proteus organisms; compounds wherein at least one of R.sup.a and R.sup.b is other than hydrogen have also shown unusually high activity against Pseudomonas organisms. Important compounds of the above type include those in which the 7.beta.-acylamido group is a syn-2-carboxymethoxy-2-(fur-2-yl)acetamido, syn-2-(2-carboxyprop-2-yloxyimino)-2-(fur-2-yl)acetamido or syn-2-(1-carboxycyclopent-1-yloxyimino)-2-(fur-2-yl)acetamido group.

  7-β-酰胺基头孢菌素，其结构中7-β-酰胺基团具有以下结构：##STR1##（其中R为噻吩基或呋喃基；R.sup.a和R.sup.b分别选自氢，C.sub.1-4烷基，C.sub.2-4烯基，C.sub.3-7环烷基，苯基，萘基，噻吩基，呋喃基，羧基，C.sub.2-5烷氧羰基和氰基，或R.sup.a和R.sup.b与它们附着的碳原子形成C.sub.3-7环烷基亚甲基或环烯基亚甲基；m和n分别为0或1，使m和n的和为0或1），表现出广谱抗生素活性，其特点是对革兰氏阴性微生物特别高效，包括产生β-内酰胺酶的微生物。这些化合物是同构体或存在至少90％的同构体和反构体的混合物，对大肠杆菌，流感嗜血杆菌和变形杆菌菌株的体外活性特别高；其中R.sup.a和R.sup.b中至少有一个不是氢的化合物也显示出对假单胞菌的异常高活性。上述类型的重要化合物包括其中7-β-酰胺基团为syn-2-羧甲氧基-2-（呋喃-2-基）乙酰胺基，syn-2-（2-羧基丙-2-氧基亚胺）-2-（呋喃-2-基）乙酰胺基或syn-2-（1-羧基环戊-1-氧基亚胺）-2-（呋喃-2-基）乙酰胺基团的化合物。